crossing96/oncoscreening huggingface dataset:
Renin-Angiotensin Inhibitors Decrease Recurrence after Transurethral Resection of Bladder Tumor in Patients with Nonmuscle Invasive Bladder Cancer.	PURPOSE: Prior reports suggest that renin-angiotensin system inhibition may decrease nonmuscle invasive bladder cancer recurrence. We evaluated whether angiotensin converting enzyme inhibitor or angiotensin receptor blocker treatment at initial surgery was associated with decreased recurrence or progression in patients with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Using an institutional bladder cancer database we identified 340 patients with data available on initial transurethral resection of bladder tumor. Progression was defined as an increase to stage T2. Cox proportional hazards models were used to evaluate associations with recurrence-free and progression-free survival. RESULTS: Median patient age was 69.6 years. During a median followup of 3 years (IQR 1.3-6.1) 200 patients (59%) had recurrence and 14 (4.1%) had stage progression. Of those patients 143 were receiving angiotensin converting enzyme inhibitor/angiotensin receptor blockers at the time of the first transurethral resection. On univariate analysis factors associated with improved recurrence-free survival included carcinoma in situ (p = 0.040), bacillus Calmette-Guérin therapy (p = 0.003) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (p = 0.009). Multivariate analysis demonstrated that patients treated with bacillus Calmette-Guérin therapy (HR 0.68, 95% CI 0.47-0.87, p = 0.002) or angiotensin converting enzyme inhibitor/angiotensin receptor blocker therapy (HR 0.61, 95% CI 0.45-0.84, p = 0.005) were less likely to experience tumor recurrence. The 5-year recurrence-free survival rate was 45.6% for patients treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers and 28.1% in those not treated with angiotensin converting enzyme inhibitor/angiotensin receptor blockers (p = 0.009). Subgroup analysis was performed to evaluate nonmuscle invasive bladder cancer pathology (Ta, T1 and carcinoma in situ) in 85 patients on bacillus Calmette-Guérin therapy alone and in 52 in whom it was combined with angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Multivariate analysis revealed that patients treated with bacillus Calmette-Guérin alone (HR 2.19, 95% CI 1.01-4.77, p = 0.04) showed worse recurrence-free survival compared to patients treated with bacillus Calmette-Guérin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (stage Ta HR 0.45, 95% CI 0.21-0.98, p = 0.04). CONCLUSIONS: Pharmacological inhibition of the renin-angiotensin system is associated with improved outcomes in patients with bladder cancer. Renin-angiotensin system inhibitor administration in nonmuscle invasive bladder cancer cases should be studied in a prospective randomized trial.	bladder
Negative Control Outcomes and the Analysis of Standardized Mortality Ratios.	In occupational cohort mortality studies, epidemiologists often compare the observed number of deaths in the cohort to the expected number obtained by multiplying person-time accrued in the study cohort by the mortality rate in an external reference population. Interpretation of the result may be difficult due to noncomparability of the occupational cohort and reference population with respect to unmeasured risk factors for the outcome of interest. We describe an approach to estimate an adjusted standardized mortality ratio (aSMR) to control for such bias. The approach draws on methods developed for the use of negative control outcomes. Conditions necessary for unbiased estimation are described, as well as looser conditions necessary for bias reduction. The approach is illustrated using data on bladder cancer mortality among male Oak Ridge National Laboratory workers. The SMR for bladder cancer was elevated among hourly-paid males (SMR = 1.9; 95% confidence interval [CI] = 1.3, 2.7) but not among monthly-paid males (SMR = 1.0; 95% CI = 0.67, 1.3). After indirect adjustment using the proposed approach, the mortality ratios were similar in magnitude among hourly- and monthly-paid men (aSMR = 2.2; 95% CI = 1.5, 3.2; and, aSMR = 2.0; 95% CI = 1.4, 2.8, respectively). The proposed adjusted SMR offers a complement to typical SMR analyses.	bladder
How to Name Papillary Tumors of the Bladder in Children: Transitional Cell Carcinoma or Papillary Urothelial Neoplasm of Low Malignant Potential?	Urinary bladder malignancies are uncommon in children. Approximately 80 children with papillary carcinoma have been described to date, presenting as papillary neoplasms of both low grade and low stage. On the basis of the 1973 World Health Organization classification, tumors were classified as transitional cell carcinoma of the urinary bladder (TCCB). Owing to more detailed histologic criteria, this term has been replaced by papillary urothelial neoplasm of low malignant potential and low-grade carcinoma of the urinary bladder in the World Health Organization-International Society of Urologic Pathology consensus classification system of urothelial neoplasms 2004. Nevertheless, TCCB still remains a common term in contemporary literature. Thus, the differences between papillary urothelial neoplasm of low malignant potential, low-grade carcinoma of the urinary bladder, and TCCB will be illustrated by means of 4 examples of pediatric patients with papillary tumors.	bladder
The Effects of Instrumentation on Urine Cytology and CK-20 Analysis for the Detection of Bladder Cancer.	OBJECTIVE: To evaluate the effects of cystoscopy on urine cytology and additional cytokeratin-20 (CK-20) staining in patients presenting with gross hematuria. PATIENTS AND METHODS: For 83 patients presenting with gross hematuria, spontaneous and instrumented paired urine samples were analyzed. Three patients were excluded. Spontaneous samples were collected within 1 hour before cystoscopy, and the instrumented samples were tapped through the cystoscope. Subsequently, patients underwent cystoscopic evaluation and imaging of the urinary tract. If tumor suspicious lesions were found on cystoscopy or imaging, subjects underwent transurethral resection or ureterorenoscopy. Two blinded uropathological reviewers (DB, KK) evaluated 160 urine samples. Reference standards were results of cystoscopy, imaging, or histopathology. RESULTS: Thirty-seven patients (46.3%) underwent transurethral resection or ureterorenoscopy procedures. In 30 patients (37.5%) tumor presence was confirmed by histopathology. The specificity of urine analysis was significantly higher for spontaneous samples than instrumented samples for both cytology alone (94% vs 72%, P = .01) and for cytology combined with CK-20 analysis (98% vs 84%, P = .02). The difference in sensitivity between spontaneous and instrumented samples was not significant for both cytology alone (40% vs 53%) and combined with CK-20 analysis (67% vs 67%). The addition of CK-20 analysis to cytology significantly increases test sensitivity in spontaneous urine cytology (67% vs 40%, P = .03). CONCLUSION: Instrumentation significantly decreases specificity of urine cytology. This may lead to unnecessary diagnostic procedures. Additional CK-20 staining in spontaneous urine cytology significantly increases sensitivity but did not improve the already high specificity. We suggest performing urine cytology and CK-20 analysis on spontaneously voided urine.	bladder
γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Mycobacteria.	PURPOSE: γ Irradiated Mycobacterium bovis bacillus Calmette-Guérin has shown in vitro and ex vivo antitumor activity. However, to our knowledge the potential antitumor capacity has not been demonstrated in vivo. We studied the in vivo potential of γ irradiated bacillus Calmette-Guérin and γ irradiated M. brumae, a saprophytic mycobacterium that was recently described as an immunotherapeutic agent. MATERIALS AND METHODS: The antitumor capacity of γ irradiated M. brumae was first investigated by analyzing the in vitro inhibition of bladder tumor cell proliferation and the ex vivo cytotoxic effect of M. brumae activated peripheral blood cells. The effect of γ irradiated M. brumae or bacillus Calmette-Guérin intravesical treatment was then compared to treatment with live mycobacteria in the orthotopic murine model of bladder cancer. RESULTS: Nonviable M. brumae showed a capacity to inhibit in vitro bladder cancer cell lines similar to that of live mycobacteria. However, its capacity to induce cytokine production was decreased compared to that of live M. brumae. γ Irradiated M. brumae could activate immune cells to inhibit tumor cell growth, although to a lesser extent than live mycobacteria. Finally, intravesical treatment with γ irradiated M. brumae or bacillus Calmette-Guérin significantly increased survival with respect to that of nontreated tumor bearing mice. Both γ irradiated mycobacteria showed lower survival rates than those of live mycobacteria but the minor efficacy of γ irradiated vs live mycobacteria was only significant for bacillus Calmette-Guérin. CONCLUSIONS: Our results show that although γ irradiated mycobacteria is less efficacious than live mycobacteria, it induces an antitumor effect in vivo, avoiding the possibility of further mycobacterial infections.	bladder
The YAP1 oncogene contributes to bladder cancer cell proliferation and migration by regulating the H19 long noncoding RNA.	BACKGROUND: Yes-associated protein 1 (YAP1) and long noncoding RNA H19 act as potent oncogenes in many human cancers, but little is known about their roles in bladder cancer or their relationship with each other. METHODS: Quantitative real-time polymerase chain reaction and western blotting were performed retrospectively on human bladder cancer specimens and on bladder cancer cell lines (UMUC-3, EJ, and 5637). YAP1 and H19 expression levels were detected and correlated with clinical and pathologic grades. To determine whether YAP1 regulates H19 expression, their genes were overexpressed or suppressed in 5637 and UMUC-3 cells. The effects of YAP1/H19 on proliferation and migration were determined by viability, colony formation, transwell migration, and wound-healing assays. RESULTS: YAP1 and H19 expression levels were markedly elevated in bladder cancer tissues and cells, and H19 expression was found to be significantly associated with YAP1 expression. Determination of their clinicopathologic significance in 40 human bladder cancer tissues showed that specimens in which YAP1 and H19 were overexpressed were associated with poorer clinicopathologic prognosis. In addition, YAP1 was found to enhance H19 expression, whereas H19 had no significant effect on YAP1 expression in bladder cancer cells. Furthermore, the results of in vitro analyses suggested that this association regulates cell proliferation and migration. CONCLUSION: Our results emphasize the importance of YAP1 and H19 in bladder cancer progression and indicate that H19, at least in part, is induced by YAP1 overexpression.	bladder
Knockdown of PLCε inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells.	Phospholipase Cε (PLCε) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCε can alter inflammatory cytokine by affecting downstream pathways. Recent studies suggest that inflammation is likely to have an important role in transitional cell carcinoma of bladder (TCCB) and cancer disease progression. Here, we showed that PLCε and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCε level was associated with the increase of p-STAT3 level. Then, knockdown of PLCε using adenovirus-shPLCε significantly decreased inflammatory cytokine (IL-6, TNF-α, IL-1β) expression and inflammation-associated gene (TLR4, MyD88, p-STAT3) expression. Furthermore, we demonstrated that PLCε knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCε exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCε-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCε as a therapeutic target for TCCB.	bladder
What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?	In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival.	bladder
Silver nanoparticles-induced cytotoxicity requires ERK activation in human bladder carcinoma cells.	Silver nanoparticles are toxic both in vitro and in vivo. We have investigated the possibility to exploit the cytotoxic potential of silver nanoparticles in T24 bladder carcinoma cells using both bare and PolyVinylPyrrolidone-coated silver nanoparticles. We show that the two types of silver nanoparticles promote morphological changes and cytoskeletal disorganization, are cytotoxic and induce cell death. These effects are due to the increased production of reactive oxygen species which are responsible, at least in part, for the sustained activation of ERK1/2. Indeed, both cytotoxicity and ERK1/2 activation are prevented by exposing the cells to the anti-oxidant N-acetylcysteine. Also blocking the ERK1/2 pathway with the MEK inhibitor PD98059 protects the cells from nanoparticles' cytotoxicity. Our findings suggest that ERK activation plays a role in silver nanoparticle-mediated cytotoxicity in T24 cells.	bladder
The C228T mutation of TERT promoter frequently occurs in bladder cancer stem cells and contributes to tumorigenesis of bladder cancer.	Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.	bladder
Radical Cystectomy for Bladder Cancer in Patients With and Without a History of Pelvic Irradiation: Survival Outcomes and Diversion-related Complications.	OBJECTIVE: To compare survival outcomes and diversion-related complications of patients with and without a history of pelvic irradiation who underwent radical cystectomy. PATIENTS AND METHODS: Three hundred sixty-four patients underwent radical cystectomy for bladder cancer (BCa) from July 2001 to September 2013. Thirty-seven patients (10%) had a history of pelvic irradiation, and 327 (90%) did not. The Kaplan-Meier method and Cox regression models were applied to evaluate survival outcomes. Diversion-related complications were tabulated. RESULTS: The proportion of non-organ-confined disease was numerically higher in irradiated than in nonirradiated patients (18 of 37 [49%] vs 117 of 327 [36%] patients, P = .1). The difference in the proportion of T4 disease between the 2 groups was statistically significant (13 of 37 [35%] irradiated vs 37 of 327 [11%] nonirradiated patients, P = .005). Pelvic lymph node dissection could not be performed in 7 of 37 irradiated patients. A nonurothelial carcinoma histology was more frequent in irradiated than in nonirradiated patients (5 of 37 [14%] vs 19 of 327 [6%], P = .003). At 3 years, BCa recurrence-free survival estimates were 70 ± 9% and 77 ± 3% (log-rank P = .5), and BCa-specific survival estimates were 64 ± 9% and 69 ± 3% (log-rank P = .4), for irradiated and nonirradiated patients, respectively. In multivariate analysis, a history of pelvic irradiation was not predictive of BCa recurrence or BCa-specific death. Rates of diversion-related complications did not differ between the 2 groups. CONCLUSION: BCa patients with a history of pelvic irradiation present with more advanced disease. Surgery remains difficult in this group of patients as pelvic lymph node dissection is omitted in approximately 1 of 5 patients. Within limitations, prior pelvic irradiation is not predictive of survival outcomes.	bladder
Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis.	Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n = 94), benign bladder lesions (n = 60), and age-matched normal controls (n = 56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P < .001). The receiver-operating characteristic curve analyses demonstrated that each one had good sensitivity and specificity for distinguishing BC patients from non-BC ones (HYAL1, 89.4 and 91.2 %; miR-210, 76.6 and 93 %; miR-96, 76.6 and 89.4 %; and lncRNA-UCA1, 91.5 and 96.5 %). There was a significant positive correlation between HYAL1 and the selected epigenetic biomarkers. The performance of this urine biomarker panel reached 100 % sensitivity and 89.5 % specificity for bladder cancer diagnosis.	bladder
Impact of adjuvant chemotherapy on patients with pathological Stage T3b and/or lymph node metastatic bladder cancer after radical cystectomy.	OBJECTIVE: To evaluate the effectiveness of adjuvant chemotherapy in patients with pathological Stage T3 bladder cancer who had undergone radical cystectomy, and to determine the prognostic survival factors for adjuvant chemotherapy treatment. METHODS: From January 1990 to October 2013, 202 patients underwent radical cystectomy and pelvic lymphadenectomy. Among them, 65 patients with non-organ-confined disease (pT3, N0-3, M0) diagnosed were investigated in this study. Thirty-one patients (48%) were treated with adjuvant chemotherapy and the remaining 34 patients (52%) were not. RESULTS: Median age of all patients was 66 years, and median follow-up was 26.1 months. For all pT3 patients, overall survival and disease-free survival times were similar in the adjuvant chemotherapy and non-adjuvant chemotherapy groups. However, in the pT3b subgroup, median overall survival (47.0 vs. 10.6 months) and median disease-free survival (35.5 vs. 5.3 months) times were significantly prolonged for those who underwent adjuvant chemotherapy (P = 0.009 and 0.025). In patients with pathological lymph node metastatic (pN+), median overall survival (30.1 vs. 6.4 months) and median disease-free survival (15.7 vs. 3.5 months) times were significantly prolonged in the adjuvant chemotherapy group (P = 0.016 and 0.027). In addition, according to multivariate analysis in pT3b and/or pN+ subgroup patients, adjuvant chemotherapy status was an independent predictive factor for overall survival and disease-free survival. CONCLUSION: Adjuvant chemotherapy did not significantly improve overall survival and disease-free survival when compared with all patients with pT3 who had received radical cystectomy in the non-adjuvant chemotherapy group. However, in the pT3b and pN+ subgroup, adjuvant chemotherapy demonstrated statistically significant benefits regarding overall survival and disease-free survival. Although these results could not support adjuvant chemotherapy use for all pT3 patients, the pT3b substage and/or pN+ may help identify patients with pT3 who could benefit from adjuvant chemotherapy.	bladder
Prognostic significance of substage and WHO classification systems in T1 urothelial carcinoma of the bladder.	PURPOSE OF REVIEW: Treatment of T1 urothelial bladder cancer (T1-BC) is challenging as risk assessment criteria for progression are lacking. Histological grade and T1 substage have been identified as important prognostic factors. Currently, no consensus exists regarding the optimal sub-staging and grading systems for T1-BC. We reviewed recent advances in the various grading and sub-staging systems and their clinical applicability. RECENT FINDINGS: Stratification by muscularis mucosae invasion is the most explored sub-staging system. Its prognostic value was established by 12/23 (52%) available studies. Importantly, muscularis mucosae identification varied substantially among pathologists. Sub-staging based on diameter of invasive carcinoma [T1 microinvasive and T1 extensive-invasive (T1m/e)] proved a more reproducible system with at least equal prognostic value. However, more study is needed to investigate interobserver variation. For nonmuscle-invasive bladder cancer grading, the 1973 and 2004 WHO classifications both provide independent prognostic information. However, remarkably few studies have investigated their applicability in T1-BC only. The available reports suggest that the 1973 WHO classification is superior to WHO 2004. SUMMARY: If multicenter studies confirm the promising results of T1m/e sub-staging, it may be incorporated in the Internation Union Against Cancer TNM classification system for urinary bladder cancer. More studies are warranted to define the optimal classification system for grade in T1-BC.	bladder